AMAZE 4: A Research Study Investigating How Well the Medicine NNC0487-0111 Helps People With Excess Body Weight and Obstructive Sleep Apnoea Treated With Positive Airway Pressure Lose Weight and Improve Sleep Apnoea (AMAZE 4)

Efficacy and Safety of NNC0487-0111 s.c. Once-weekly in Participants With Overweight or Obesity, and Obstructive Sleep Apnoea Treated With Positive Airway Pressure (AMAZE 4)

This study is being done to look at the efficacy and safety of NNC0487-0111 in participants with overweight or obesity, and obstructive sleep apnoea treated with positive airway pressure. There are 2 study treatments in this study taken as injections under the skin once a week. Participants will either get NNC0487-0111, (the treatment being tested) or Placebo (a treatment that has no active medicine in it) and which treatment participants get is decided by chance.

Study Overview

• Status: Recruiting
• Conditions: Obesity; Overweight; Obstructive Sleep Apnoea
• Intervention / Treatment: Drug: NNC0487-0111; Drug: Placebo (matched to NNC0487-0111)

• Study Type: Interventional
• Enrollment (Estimated): 300
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Novo Nordisk; Phone Number: (+1) 866-867-7178; Email: clinicaltrials@novonordisk.com

Study Locations

• Australia
  • New South Wales
    • Macquarie Park, New South Wales, Australia, 2113
      • Recruiting
      • Woolcock Institute
  • Queensland
    • Birtinya, Queensland, Australia, 4575
      • Recruiting
      • University of Sunshine Coast - Vitality Village
    • South Brisbane, Queensland, Australia, 4101
      • Not yet recruiting
      • Mater Research - RIO Clinical Trials Unit
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Recruiting
      • Nightingale Research
  • Western Australia
    • Crawley, Western Australia, Australia, 6009
      • Recruiting
      • University of Western Australia - Centre for Sleep Science
• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100044
      • Not yet recruiting
      • Peking University People's Hospital-Endocrinology
  • Guangdong
    • Shenzhen, Guangdong, China, 518020
      • Not yet recruiting
      • Shenzhen People's Hospital-Sleep Medicine Department
  • Henan
    • Luoyang, Henan, China, 471003
      • Not yet recruiting
      • The First Affiliated Hospital of Henan University of Science and Technology-Endocrinology
  • Jiangsu
    • Nanjing, Jiangsu, China, 210011
      • Not yet recruiting
      • The Second Affiliated Hospital of Nanjing Medical University-Endocrinology
  • Tianjin Municipality
    • Tianjin, Tianjin Municipality, China, 300052
      • Not yet recruiting
      • Tianjin Medical University General Hospital-Respiratory
• Germany
  • Bochum, Germany, 44787
    • Recruiting
    • Siteworks GmbH Bochum
  • Hamburg, Germany, 22607
    • Recruiting
    • Wendisch - Dahl Hamburg - DZHW
  • Hanover, Germany, 30449
    • Recruiting
    • Siteworks GmbH Hannover
  • Karlsruhe, Germany, 76137
    • Recruiting
    • Siteworks GmbH Karlsruhe
  • Münster, Germany, 48145
    • Recruiting
    • Institut für Diabetesforschung GmbH Münster - Dr. med. Rose
  • Schleswig, Germany, 24837
    • Recruiting
    • Siteworks GmbH - Prüfzentrum Schleswig | RespiRatio
• India
  • Jaipur, India, 302039
    • Not yet recruiting
    • Asthma Bhawan
  • Andhra Pradesh
    • Guntur, Andhra Pradesh, India, 522004,
      • Withdrawn
      • Guntur Government medical College
    • Vijayawada, Andhra Pradesh, India, 520008
      • Not yet recruiting
      • Government Siddhartha Medical College & Government General Hospital, Vijayawada
  • Karnataka
    • Bengaluru, Karnataka, India, 560074
      • Not yet recruiting
      • Rajarajeswari Medical College and Hospital
  • Kerala
    • Kochi, Kerala, India, 682041
      • Not yet recruiting
      • Amrita Institute Of Medical Sciences & Research Centre
  • Maharashtra
    • Mumbai, Maharashtra, India, 401107
      • Not yet recruiting
      • Bhaktivedanta Hospital & Research Institute
    • Nagpur, Maharashtra, India, 440010
      • Not yet recruiting
      • Asian Kidney Hospital And Medical Centre
  • National Capital Territory of Delhi
    • New Delhi, National Capital Territory of Delhi, India, 110029
      • Not yet recruiting
      • Vardhaman Mahavir Medical College & Safdarjung Hospital
  • New Delhi
    • Delhi, New Delhi, India, 110029
      • Not yet recruiting
      • All India Institute of Medical Sciences_Delhi
  • Odisha
    • Bhubaneswar, Odisha, India, 751019
      • Not yet recruiting
      • All India Institute of Medical Sciences (AIIMS), Bhubaneswar
  • Telangana
    • Hyderabad, Telangana, India, 500084
      • Withdrawn
      • Yashoda Hospital
  • Uttar Pradesh
    • Lucknow, Uttar Pradesh, India, 226006
      • Not yet recruiting
      • Midland Healthcare & Research Center
  • West Bengal
    • Kolkata, West Bengal, India, 700054
      • Not yet recruiting
      • Apollo Multispeciality Hospital, Kolkata
• Japan
  • Fukuoka, Japan, 814-0180
    • Not yet recruiting
    • Fukuoka University Hospital_Respiratory Medicine
  • Hiroshima, Japan, 730-0051
    • Recruiting
    • Chatani NeuroSleep Clinic_Neurology
  • Kumamoto, Japan, 862-0954
    • Recruiting
    • Kuwamizu Hospital_Internal Medicine
  • Okinawa, Japan, 901-2132
    • Recruiting
    • Nakamura Clinic_Pulmonology
  • Osaka, Japan, 532-0003
    • Recruiting
    • Osaka Kaisei Hospital_Sleep Medical Center
  • Sapporo-shi, Hokkaido, Japan, 062-0931
    • Recruiting
    • KKR Sappro Medical Center_Respiratory Medicine
  • Shizuoka, Japan, 436-8555
    • Not yet recruiting
    • Chutoen General Medical Center_Neurology
  • Tokyo, Japan, 103-0027
    • Not yet recruiting
    • Tokyo-Eki Center-building Clinic_Internal Medicine
  • Tokyo, Japan, 113-8431
    • Not yet recruiting
    • Juntendo University Hospital_Cardiovascular Biology And Medicine
  • Tokyo, Japan, 193-0811
    • Recruiting
    • Tokyo Tenshi Hospital_Internal medicine
• Poland
  • Gdansk, Poland, 80-214
    • Not yet recruiting
    • Uniwersyteckie Centrum Kliniczne
  • Gdansk, Poland, 80-546
    • Not yet recruiting
    • Centrum Badan Klinicznych PI-House sp. z o.o.
  • Krakow, Poland, 30-901
    • Not yet recruiting
    • 5 Wojskowy Szpital Kliniczny z Polikliniką-Samodzielny Publiczny Zakład Opieki Zdrowotnej w Krakowie
  • Krakow, Poland, 31-202
    • Withdrawn
    • Krakowski Szpital Specjalistyczny im. Jana Pawla II
  • Poznan, Poland, 60-569
    • Not yet recruiting
    • Uniwersytecki Szpital Kliniczny w Poznaniu
  • Warsaw, Poland, 02-507
    • Not yet recruiting
    • PANSTWOWY INSTYTUT MEDYCZNY MSWiA
  • Warsaw, Poland, 00-124
    • Not yet recruiting
    • Gyncentrum Sp. z o. o.
  • Warsaw, Poland, 01-138
    • Not yet recruiting
    • National Institute Of Tuberculosis And Lung Diseases - Instytut Gruźlicy i Chorób Płuc
  • Warsaw, Poland, 02-677
    • Not yet recruiting
    • ETG Warszawa Sp. z o.o.
  • Dolnoslaskie Voivodeship
    • Wroclaw, Dolnoslaskie Voivodeship, Poland, 50-981
      • Not yet recruiting
      • 4 Wojskowy Szpital Kliniczny Z Poliklinika Samodzielny Publiczny Zaklad Opieki Zdrowotnej We Wroclawiu
• Spain
  • Barcelona, Spain, 08035
    • Not yet recruiting
    • Hospital Vall d'Hebron
  • Castilleja de la Cuesta, Spain, 41950
    • Recruiting
    • Hospital Vithas Sevilla
  • Lleida, Spain, 25198
    • Recruiting
    • Hospital Univ. de Santa María de Lleida
  • Logroño, Spain, 26006
    • Not yet recruiting
    • Hospital Universitario San Pedro
  • Madrid, Spain, 28034
    • Recruiting
    • Hospital Ramon y Cajal
  • Madrid, Spain, 28036
    • Recruiting
    • Instituto de Investigaciones del Sueño
  • Vitoria-Gasteiz, Spain, 01004
    • Recruiting
    • Hospital Universitario de Araba
  • Castille-La Mancha
    • Guadalajara, Castille-La Mancha, Spain, 19002
      • Recruiting
      • Hospital Universitario de Guadalajara
  • Madrid
    • Pozuelo de Alarcón, Madrid, Spain, 28223
      • Recruiting
      • H.U. Quirónsalud Madrid
• Taiwan
  • Chiayi City, Taiwan, 600
    • Not yet recruiting
    • Ditmanson Medical Foundation Chia-Yi Christian Hospital
  • Taipei, Taiwan, 106
    • Not yet recruiting
    • Cathay General Hospital
  • Taipei, Taiwan, 110
    • Not yet recruiting
    • Taipei Medical University Hospital
  • Taipei, Taiwan, 116
    • Not yet recruiting
    • Taipei Municipal Wan Fang Hospital_Division of Otorhinolaryngology
  • Taoyuan, Taiwan, 333
    • Not yet recruiting
    • Chang Gung Memorial Hospital, Linkou
• Turkey (Türkiye)
  • Alanya/ Antalya, Turkey (Türkiye), 07400
    • Not yet recruiting
    • T.C. Sağlık Bakanlığı Alaaddin Keykubat Üniversitesi Alanya Eğitim ve Araştırma Hastanesi-Göğüs Hastalıkları
  • Maltepe/İstanbull, Turkey (Türkiye), 34843
    • Recruiting
    • İstanbul İl Sağlik Müdürlüğü Süreyyapaşa Göğüs Hastaliklari Ve Göğüs Cerrahisi Eğitim Ve Araştirma Hastanesi
  • Merkez/Battalgazi/Malatya, Turkey (Türkiye), 44280
    • Recruiting
    • İnönü Üniversitesi Turgut Özal Tıp Merkezi Hastanesi- Göğüs Hastalıkları
  • Merkez/Çorum, Turkey (Türkiye), 19040
    • Recruiting
    • Hitit Üniversitesi Çorum Erol Olçok Eğitim ve Araştırma Hastanesi-Göğüs Hastalıkları
  • Yenimahalle / Ankara, Turkey (Türkiye), 06170
    • Recruiting
    • Ankara Etlik Şehir Hastanesi-Göğüs Hastalıkları
  • Yuregir/Adana, Turkey (Türkiye), 01060
    • Recruiting
    • Adana Şehir Eğitim ve Araştırma Hastanesi-Dahiliye
  • Yıldırım/Bursa, Turkey (Türkiye), 16310
    • Recruiting
    • Bursa Yüksek İhtisas Eğitim ve Araştırma Hastanesi-Göğüs Hastalıkları
  • Zeytinburnu/İstanbul, Turkey (Türkiye), 34020
    • Recruiting
    • Yedikule Göğüs Hastalıkları ve Göğüs Cerrahisi Eğitim ve Araştırma Hastanesi
• United States
  • Arizona
    • Gilbert, Arizona, United States, 85297
      • Recruiting
      • Dignity Health, Mercy Gilbert
  • Florida
    • Bradenton, Florida, United States, 34209
      • Recruiting
      • DM Clinical
    • Naples, Florida, United States, 34102
      • Recruiting
      • Essence MD Research
    • West Palm Beach, Florida, United States, 33409
      • Recruiting
      • Palm Beach Research Center
  • Georgia
    • Atlanta, Georgia, United States, 30328
      • Recruiting
      • NeuroTrials Research, Inc.
    • Lawrenceville, Georgia, United States, 30046
      • Recruiting
      • Physicians Research Associates
  • Illinois
    • Chicago, Illinois, United States, 60634
      • Recruiting
      • Chicago Research Center, Inc
  • New York
    • New York, New York, United States, 10021
      • Not yet recruiting
      • Weil Cornell Medicine
  • North Dakota
    • Fargo, North Dakota, United States, 58104
      • Recruiting
      • Lillestol Research LLC
  • Ohio
    • Cincinnati, Ohio, United States, 45212
      • Recruiting
      • CTI Clinical Research Center
  • Pennsylvania
    • DuBois, Pennsylvania, United States, 15801
      • Not yet recruiting
      • Clinical Research Associates of Central PA, LLC
  • South Carolina
    • Columbia, South Carolina, United States, 29201
      • Recruiting
      • Bogan Sleep Consultants, LLC
  • Texas
    • DeSoto, Texas, United States, 75115
      • Recruiting
      • Epic Medical Research
    • El Paso, Texas, United States, 79912
      • Recruiting
      • Advanced Neurology Epilepsy and Sleep Center ANESC
    • El Paso, Texas, United States, 79912
      • Recruiting
      • Biorhythms Center for Integrative Sleep Medicine
    • Houston, Texas, United States, 77089
      • Recruiting
      • Houston Pulmonary Medicine Associates, PA
    • San Antonio, Texas, United States, 78229
      • Recruiting
      • Sleep Therapy Research Center
    • Sugar Land, Texas, United States, 77478
      • Recruiting
      • Tricoastal Sleep Center
  • Washington
    • Renton, Washington, United States, 98057
      • Recruiting
      • Rainier Clin Res Ctr Inc
    • Seattle, Washington, United States, 98104
      • Recruiting
      • Seattle Clinical Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Male or female (sex at birth)
• Age 18 years or above at the time of signing informed consent
• Previously diagnosed moderate-to-severe OSA with an AHI ≥ 15, as diagnosed with polysomnography (PSG), home sleep apnoea test (HSAT), or other method that meets local guidelines prior to screening

Key Exclusion Criteria:

• Glycated haemoglobin (HbA1c) ≥ 6.5% (48 mmol/mol) as measured by the central laboratory at screening
• History of type 1 or type 2 diabetes mellitus as declared by the participant or reported in the medical records
• Any planned or previous surgery within 90 days prior to screening for sleep apnoea, including septoplasty, turbinoplasty, or other ear, nose, and throat surgeries, including tonsillectomy and adenoidectomy
• Significant craniofacial abnormalities that may affect breathing at baseline, for example Treacher Collins syndrome and Pierre Robin Sequence
• Treatment with glucagon-like-peptide-1 (GLP-1) receptor agonist (RA), dual GLP-1/gastric inhibitory peptide (GIP) RAs (or any other GLP-1 based treatment) or amylin analogues before screening

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Participants will receive placebo matched to NNC0487-0111 subcutaneously once weekly as an adjunct to a reduced-calorie diet and increased physical activity.	Drug: Placebo (matched to NNC0487-0111); Placebo matched to NNC0487-0111 will be administered subcutaneously using PDS290 pre-filled pen-injectors to one of the body parts: thigh, abdomen or upper arm.
Experimental: NNC0487-0111; Participants will be randomized to receive 1 of the 2 dose levels of NNC0487-0111 subcutaneously once weekly as an adjunct to a reduced-calorie diet and increased physical activity.	Drug: NNC0487-0111; NNC0487-0111 will be administered subcutaneously using PDS290 pre-filled pen-injectors to one of the body parts: thigh, abdomen or upper arm.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relative change in body weight	Measured as percentage (%) change in body weight.	From baseline (week 0) to (week 80)
Change in apnoea-hypopnoea index (AHI)	Measured as events/hour.	From baseline (week 0) to (week 80)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in waist circumference	Measured as centimetre (cm).	From baseline (week 0) to (week 80)
Change in systolic blood pressure (SBP)	Measured as millimetre of mercury (mmHg).	From baseline (week 0) to (week 80)
Change in diastolic blood pressure (DBP)	Measured as mmHg.	From baseline (week 0) to (week 80)
Change in high-sensitivity C-reactive protein (hsCRP)	Measured as ratio to baseline.	From baseline (week 0) to (week 80)
Change in glycated haemoglobin (HbA1c)	Measured as percentage (%) of HbA1c.	From baseline (week 0) to (week 80)
Number of TEAEs leading to permanent treatment discontinuation	Measured as events.	From baseline (week 0) to week 84
Relative change in AHI	Measured as percentage change in AHI.	From baseline (week 0) to (week 80)
Achievement of 50% reduction in AHI (Yes/No)	Measured as number of participant.	From baseline (week 0) to (week 80)
Achievement of: AHI less than (<) 5	Measured as number of participants.	From baseline (week 0) to (week 80)
Achievement of: AHI 5-14 with Epworth Sleepiness Scale (ESS) ≤ 10 (Yes/No)	Measured as number of participants.	From baseline (week 0) to (week 80)
Change in sleep apnoea specific hypoxic burden (SASHB)	measured as %min/h (percentage minutes per hour).	From baseline (week 0) to (week 80)
Change in ESS score	Measured as score on a scale. ESS measures the level of daytime sleepiness or average sleep propensity. The measure consists of 8 items yielding one total score. Total score ranges from 0-24. Higher scores indicate higher sleepiness or average sleep propensity in daily life.	From baseline (week 0) to (week 80)
Change in Patient-Reported Outcomes Measurement Information System (PROMIS) Short Form v1.0 Sleep-Related Impairment 8a score	Measured as score on a scale. PROMIS-SRI measures perceptions of alertness, sleepiness, and tiredness during usual waking hours, and the perceived functional impairments during wakeful-ness associated with sleep problems or impaired alertness. The measure consists of 8 items each rated on a 5-point scale ranging from "not at all" to "very much". Individual item scores will be combined and converted to a T-score using a response pattern scoring approach. The T-score standardises the raw score to a distribution with a mean of 50 and standard deviation of 10. Total score (T-score range): Sleep-related impairment (ranging approximately from 30-80.1). Higher scores indicate more sleep-related impairment.	From baseline (week 0) to (week 80)
Change in PROMIS Short Form v1.0 Sleep Disturbance 8b score	Measured as score on a scale. PROMIS-SD measures perceptions of sleep quality, sleep depth, and restoration associated with sleep. The measure consists of 8 items each rated on a 5-point scale ranging from "not at all" to "very much," "never" to "always," or "very poor" to "very good". Individual item scores will be combined and converted to a T-score using a response pattern scoring approach. The T-score standardises the raw score to a distribution with a mean of 50 and standard deviation of 10. Total score (T-score range): Sleep disturbance (ranging approximately from 30-80.1). Higher scores indicate more sleep disturbance.	From baseline (week 0) to (week 80)
Change in body weight	Measured as kilogram (Kg).	From baseline (week 0) to (week 80)
Change in body mass index (BMI)	Measured as kilograms per meter square (kg/m^2).	From baseline (week 0) to (week 80)
Improvement in obstructive sleep apnoea (OSA) severity category: AHI < 5/hour = normal (Yes/No)	Measured as number of participants.	From baseline (week 0) to (week 80)
Improvement in OSA severity category: ≥ 5 and < 15/hour = mild (Yes/No)	Measured as number of participants.	From baseline (week 0) to (week 80)
Improvement in OSA severity category: ≥ 15 and < 30/hour = moderate (Yes/No)	Measured as number of participants.	From baseline (week 0) to (week 80)
Improvement in OSA severity category: ≥ 30/hour = severe (Yes/No)	Measured as number of participants.	From baseline (week 0) to (week 80)
Withdrawal of positive airway pressure (PAP) therapy (Yes/No)	Measured as number of participants.	From baseline (week 0) to (week 80)
Change in neck circumference	Measured as cm.	From baseline (week 0) to (week 80)
Change in Total cholesterol	Measured as ratio to baseline.	From baseline (week 0) to (week 80)
Change in High-density lipoprotein (HDL) cholesterol	Measured as ratio to baseline.	From baseline (week 0) to (week 80)
Change in Low-density lipoprotein (LDL) cholesterol	Measured as ratio to baseline.	From baseline (week 0) to (week 80)
Change in Very low-density lipoprotein (VLDL) cholesterol	Measured as ratio to baseline.	From baseline (week 0) to (week 80)
Change in Non-HDL cholesterol	Measured as ratio to baseline.	From baseline (week 0) to (week 80)
Change in Triglycerides	Measured as ratio to baseline.	From baseline (week 0) to (week 80)
Change in fasting plasma glucose	Measured as millimoles per litre (mmol/L).	From baseline (week 0) to (week 80)
Number of Treatment emergent adverse events (TEAEs)	Measured as events.	From baseline (week 0) to week 84
Number of Treatment emergent serious adverse events (TESAEs)	Measured as Events.	From baseline (week 0) to week 84

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S
• Investigators: Study Director: Clinical Transparency dept. 2834, Novo Nordisk A/S

Study record dates

Study Major Dates

• Study Start (Actual): May 5, 2026
• Primary Completion (Estimated): June 26, 2028
• Study Completion (Estimated): August 21, 2028

Study Registration Dates

• First Submitted: April 30, 2026
• First Submitted That Met QC Criteria: April 30, 2026
• First Posted (Actual): May 6, 2026

Study Record Updates

• Last Update Posted (Actual): May 22, 2026
• Last Update Submitted That Met QC Criteria: May 19, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Nutrition Disorders; Overnutrition; Body Weight; Respiratory Tract Diseases; Respiration Disorders; Sleep Wake Disorders; Apnea; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Apnea Syndromes; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Overweight; Obesity; Sleep Apnea, Obstructive
• Other Study ID Numbers: NN9490-8293; U1111-1313-6538 (Other Identifier: World Health Organization (WHO)); 2024-520443-16 (Other Identifier: European Medical Agency (EMA))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: According to the Novo Nordisk disclosure commitment on novonordisk-trials.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No